Expression and functional study of extracellular BMP antagonists during the morphogenesis of the digits and their associated connective tissues

The purpose of this study is to gain insight into the role of BMP signaling in the diversification of the embryonic limb mesodermal progenitors destined to form cartilage, joints, and tendons. Given the importance of extracellular BMP modulators in in vivo systems, we performed a systematic search o...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e60423
Main Authors: Lorda-Diez, Carlos I, Montero, Juan A, Rodriguez-Leon, Joaquin, Garcia-Porrero, Juan A, Hurle, Juan M
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Avian Proteins - genetics
Avian Proteins - metabolism
Biology
Biomarkers - metabolism
Bone morphogenetic proteins
Bone Morphogenetic Proteins - antagonists & inhibitors
Bone Morphogenetic Proteins - physiology
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cartilage
Cartilage, Articular - embryology
Cartilage, Articular - metabolism
Cell death
Cell Proliferation
Cells, Cultured
Cellular signal transduction
Chick Embryo
Chordin
Connective tissues
Digits
Embryos
Extremities - embryology
Follistatin
Follistatin - genetics
Follistatin - metabolism
Gastrulation
Gene expression
Gene Expression Regulation, Developmental
Gene regulation
Genetic aspects
Glycoproteins - genetics
Glycoproteins - metabolism
Health aspects
Histology
Hybridization
In Situ Hybridization
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
Kinases
Laboratory animals
Modulators
Morphogenesis
Morphogenesis - genetics
Mutation
Noggin protein
Organ Specificity
Proteins
Regeneration (Biology)
Signal Transduction
Signaling
Smad Proteins - genetics
Smad Proteins - metabolism
SOST protein
Specialization
Tendons
Tendons - embryology
Tendons - metabolism
Tissues
Transcriptome
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Summary:The purpose of this study is to gain insight into the role of BMP signaling in the diversification of the embryonic limb mesodermal progenitors destined to form cartilage, joints, and tendons. Given the importance of extracellular BMP modulators in in vivo systems, we performed a systematic search of those expressed in the developing autopod during the formation of the digits. Here, we monitored the expression of extracellular BMP modulators including: Noggin, Chordin, Chordin-like 1, Chordin-like 2, Twisted gastrulation, Dan, BMPER, Sost, Sostdc1, Follistatin, Follistatin-like 1, Follistatin-like 5 and Tolloid. These factors show differential expression domains in cartilage, joints and tendons. Furthermore, they are induced in specific temporal patterns during the formation of an ectopic extra digit, preceding the appearance of changes that are identifiable by conventional histology. The analysis of gene regulation, cell proliferation and cell death that are induced by these factors in high density cultures of digit progenitors provides evidence of functional specialization in the control of mesodermal differentiation but not in cell proliferation or apoptosis. We further show that the expression of these factors is differentially controlled by the distinct signaling pathways acting in the developing limb at the stages covered by this study. In addition, our results provide evidence suggesting that TWISTED GASTRULATION cooperates with CHORDINS, BMPER, and NOGGIN in the establishment of tendons or cartilage in a fashion that is dependent on the presence or absence of TOLLOID.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0060423